Sry-related HMG-BOX gene 10, (SOX-10), a nuclear transcription factor that participates in neural crest development and in the specification and differentiation of cells of melanocytic lineage, has been recently shown to be a sensitive marker of melanoma. SOX-10 nuclear expression was found in virtually all cases of melanomas (97%) and about half of cases of malignant peripheral nerve sheath tumors (49%). In sentinel node, SOX-10 is positive in metastatic melanomas and nodal capsular nevus but not in dendritic cells, which usually express S100 protein. SOX-10 is moderately to strongly positive in desmoplastic or spindle cell melanomas, which is usually negative for HMB-45, Melan-A or even S-100. SOX-10 is diffusely expressed in schwannomas, neurofibromas, sustentacular cells of pheochromocytomas and paragangliomas. SOX-10 reaction is not identified in any other mesenchymal and epithelial tumors except for myoepitheliomas and diffuse astrocytomas.